Morning Versus Evening Dosing of Antihypertensive Medications: A Pilot Study to Assess Feasibility and Efficacy
| Status: | Completed |
|---|---|
| Conditions: | High Blood Pressure (Hypertension) |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 19 - 80 |
| Updated: | 12/31/2017 |
| Start Date: | November 2013 |
| End Date: | April 17, 2015 |
Evening Dosing of Antihypertensive Medications in Chronic Kidney Disease Patients - A Pilot Study
Hypertension is a major risk factor for cardiovascular and renal disease, and a leading cause
of premature mortality worldwide. Ambulatory blood pressure (BP) monitoring (ABPM) allows for
assessment of BP throughout the day and night. Of all the BP measurements, nighttime systolic
BP appears to be the best predictor of cardiovascular disease and all-cause mortality.
Importantly, elevated nighttime BP is a modifiable risk factor; evening dosing of
antihypertensive medications lower nighttime BP and reduces proteinuria. In a large,
randomized controlled trial, evening dosing of antihypertensive medications reduced the
hazard rate for major cardiovascular events by 67%. Findings were similar in the subgroup of
participants with chronic kidney disease (CKD). However, this single-center study was
designed to evaluate cardiovascular outcomes, not progression of CKD. The long-term effect of
nighttime dosing of antihypertensive medications on progression of CKD is unknown.
To address this important gap in knowledge, the investigators plan to conduct a pragmatic,
randomized controlled trial. 3600 participants at risk for progression of CKD who are taking
≥1 antihypertensive medication once daily will be randomized to morning versus evening dosing
of at least one antihypertensive medication. The purpose of the current study is to obtain
pilot data demonstrating the feasibility of the trial and the efficacy of the intervention.
of premature mortality worldwide. Ambulatory blood pressure (BP) monitoring (ABPM) allows for
assessment of BP throughout the day and night. Of all the BP measurements, nighttime systolic
BP appears to be the best predictor of cardiovascular disease and all-cause mortality.
Importantly, elevated nighttime BP is a modifiable risk factor; evening dosing of
antihypertensive medications lower nighttime BP and reduces proteinuria. In a large,
randomized controlled trial, evening dosing of antihypertensive medications reduced the
hazard rate for major cardiovascular events by 67%. Findings were similar in the subgroup of
participants with chronic kidney disease (CKD). However, this single-center study was
designed to evaluate cardiovascular outcomes, not progression of CKD. The long-term effect of
nighttime dosing of antihypertensive medications on progression of CKD is unknown.
To address this important gap in knowledge, the investigators plan to conduct a pragmatic,
randomized controlled trial. 3600 participants at risk for progression of CKD who are taking
≥1 antihypertensive medication once daily will be randomized to morning versus evening dosing
of at least one antihypertensive medication. The purpose of the current study is to obtain
pilot data demonstrating the feasibility of the trial and the efficacy of the intervention.
Background Hypertension is a major risk factor for cardiovascular and renal disease, and a
leading cause of premature mortality worldwide. Early hypertension studies showed that
treating elevated blood pressure (BP) reduces patients' risk of cardiovascular disease and
all-cause mortality. In subsequent research, patients achieved greater improvement in
cardiovascular outcomes when their treatment was aimed at a moderate systolic BP target
(<150mmHg) than at higher targets. Although observational data suggest that even lower BP
targets may be beneficial, this has not been seen in randomized trials; instead, "intense"
treatment of hypertension (i.e., to a target systolic BP <120mmHg) was found to have no
effect on participants' risk for renal disease, cardiovascular disease, or all-cause
mortality. Similarly negative findings were reported in studies that enrolled participants
with chronic kidney disease (CKD) and diabetes; all failed to demonstrate a benefit to
intensive lowering of clinic BP.
One potential explanation for this apparent lack of benefit of intense BP targets is that the
study protocols targeted reductions in clinic BP rather than ambulatory BP. Ambulatory BP
monitoring (ABPM) allows for assessment of BP throughout the day and night. Of all the BP
measurements, nighttime systolic BP appears to be the best predictor of cardiovascular
disease and all-cause mortality. In fact, in most observational studies, clinic BP is no
longer a predictor of adverse events after adjusting for nighttime BP. Importantly, elevated
nighttime BP is a modifiable risk factor; evening dosing of antihypertensive medications
lower nighttime BP and reduces proteinuria. In a large, randomized controlled trial, evening
dosing of antihypertensive medications reduced the hazard rate for major cardiovascular
events by 67%. Findings were similar in the subgroup of participants with CKD. However, this
single-center study was designed to evaluate cardiovascular outcomes, not progression of CKD.
The long-term effect of nighttime dosing of antihypertensive medications on progression of
CKD is unknown.
To address this important gap in knowledge, the investigators plan to conduct a pragmatic,
randomized controlled trial. 3600 participants at risk for progression of CKD who are taking
≥1 antihypertensive medication once daily will be randomized to morning versus evening dosing
of at least one antihypertensive medication. The purpose of the proposed study is to obtain
pilot data demonstrating the feasibility of the trial and the efficacy of the intervention.
Overview of Trial Design The study will be conducted in the renal clinic at University of
Minnesota Medical Center (UMMC). Eligible patients will have chronic kidney disease and be
taking a once daily antihypertensive medication. Participants will be randomized to receive
their once daily antihypertensive medication in the morning or the evening. Medication
therapy management with a focus on antihypertensive medications will take place at the time
of a clinic visit or via phone after the clinic visit. Adherence to medications will be
assessed 3-6 weeks after the clinic visit.
Objective The primary objective of this pilot study is to demonstrate 1) the feasibility of a
simple randomized trial and 2) the efficacy of medication therapy management for assigning
participants to take a once daily antihypertensive medication either in the morning or in the
evening.
leading cause of premature mortality worldwide. Early hypertension studies showed that
treating elevated blood pressure (BP) reduces patients' risk of cardiovascular disease and
all-cause mortality. In subsequent research, patients achieved greater improvement in
cardiovascular outcomes when their treatment was aimed at a moderate systolic BP target
(<150mmHg) than at higher targets. Although observational data suggest that even lower BP
targets may be beneficial, this has not been seen in randomized trials; instead, "intense"
treatment of hypertension (i.e., to a target systolic BP <120mmHg) was found to have no
effect on participants' risk for renal disease, cardiovascular disease, or all-cause
mortality. Similarly negative findings were reported in studies that enrolled participants
with chronic kidney disease (CKD) and diabetes; all failed to demonstrate a benefit to
intensive lowering of clinic BP.
One potential explanation for this apparent lack of benefit of intense BP targets is that the
study protocols targeted reductions in clinic BP rather than ambulatory BP. Ambulatory BP
monitoring (ABPM) allows for assessment of BP throughout the day and night. Of all the BP
measurements, nighttime systolic BP appears to be the best predictor of cardiovascular
disease and all-cause mortality. In fact, in most observational studies, clinic BP is no
longer a predictor of adverse events after adjusting for nighttime BP. Importantly, elevated
nighttime BP is a modifiable risk factor; evening dosing of antihypertensive medications
lower nighttime BP and reduces proteinuria. In a large, randomized controlled trial, evening
dosing of antihypertensive medications reduced the hazard rate for major cardiovascular
events by 67%. Findings were similar in the subgroup of participants with CKD. However, this
single-center study was designed to evaluate cardiovascular outcomes, not progression of CKD.
The long-term effect of nighttime dosing of antihypertensive medications on progression of
CKD is unknown.
To address this important gap in knowledge, the investigators plan to conduct a pragmatic,
randomized controlled trial. 3600 participants at risk for progression of CKD who are taking
≥1 antihypertensive medication once daily will be randomized to morning versus evening dosing
of at least one antihypertensive medication. The purpose of the proposed study is to obtain
pilot data demonstrating the feasibility of the trial and the efficacy of the intervention.
Overview of Trial Design The study will be conducted in the renal clinic at University of
Minnesota Medical Center (UMMC). Eligible patients will have chronic kidney disease and be
taking a once daily antihypertensive medication. Participants will be randomized to receive
their once daily antihypertensive medication in the morning or the evening. Medication
therapy management with a focus on antihypertensive medications will take place at the time
of a clinic visit or via phone after the clinic visit. Adherence to medications will be
assessed 3-6 weeks after the clinic visit.
Objective The primary objective of this pilot study is to demonstrate 1) the feasibility of a
simple randomized trial and 2) the efficacy of medication therapy management for assigning
participants to take a once daily antihypertensive medication either in the morning or in the
evening.
Inclusion Criteria:
1. Patients with moderate to severe kidney disease, defined as:
1. Estimated glomerular filtration rate 20-45 mls/min/1.73m2; or
2. Estimated glomerular filtration rate: 45-60 mls/min/1.73m2 with proteinuria
defined by either a urine albumin to creatinine ratio >300mg/g or a urine protein
to creatinine ratio >500mg/g.
2. Age 19-80 years
3. Taking one or more non-diuretic antihypertensive medication once daily
4. Appointment at the University of Minnesota Medical Center Renal Clinic.
Exclusion Criteria:
1. Pregnant women
2. Patients that are difficult to follow-up with: prisoners, non-English speakers
3. Patients with adherence difficulty: Mentally disabled, emotionally disabled,
developmentally disabled, impaired decision making capacity.
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